The miR-29 Family in Virus-Associated Cancers: Mechanisms, Biomarkers, and Therapeutic Opportunities

The miR-29 family (miR-29a, miR-29b, and miR-29c) demonstrates context-depend-ent roles in cancers associated with oncogenic viruses (HPV, HBV/HCV, EBV, and HTLV-1), which collectively contribute to 15-20% of human malignancies. This comprehensive review ex-amines evidence that miR-29 primarily functions as a tumor suppressor by targeting DNMT3A, PTEN, and MCL-1, thereby regulating proliferation, apoptosis, and metastasis, though it exhibits paradoxical oncogenic activity in specific contexts, such as HBV-related Hepatocellular Carci-noma (HCC). Clinical data reveal virus-specific expression patterns: miR-29a is consistently downregulated in HPV-driven cervical tissues (progressively from CIN2/3 to invasive carci-noma), but circulating miR-29 members show diagnostic utility in viral hepatocellular carcinoma. The family displays dual roles in EBV pathogenesis, suppressing Burkitt's lymphoma through TCL1 inhibition yet promoting nasopharyngeal carcinoma metastasis via extracellular matrix dis-ruption. Current evidence supports miR-29's potential as a biomarker across multiple virus-asso-ciated cancers, with clinical utility in risk stratification and disease monitoring. While preclinical studies demonstrate that miR-29 restoration can inhibit tumor progression and reduce fibrosis in cell and animal models, significant challenges remain in delivery optimization and context-spe-cific application before clinical translation. Longitudinal validation studies and standardized de-tection methodologies are needed to establish the precise diagnostic and therapeutic value of miR-29 in viral oncology.